The deaths of at least two patients have been linked to an effective but toxic drug for rheumatoid arthritis, despite an earlier safety warning to the NHS after some 25 deaths and 26 cases of serious harm in England in a decade.

Doctors are again being strongly urged to advise patients of the risk of lung disorders associated with oral methotrexate and to tell them to seek medical attention if they develop breathlessness, a dry cough or fever.

Families of the two recent cases told safety watchdogs their relatives had not sought help and that advice had not been provided by those prescribing the drug.

Methotrexate, also used for the treatment of the skin complaint psoriasis, is taken by about 50,000 patients outside hospitals, where it is used to treat patients with cancers and blood disorders.

It is said to be a good drug with a good safety profile when taken at the right frequency, right dose and with appropriate monitoring. But a number of factors make mistakes possible. There have been 137 safety incidents relating to the drug, which is one of only six out of about 13,000 licensed medicines that are taken weekly.

The manufacturers have already changed the shape of tablets so that it is easier to recognise different dosages. Concerns that the drug might be taken daily, that patients were not being given enough information and that there was not sufficient monitoring prompted the National Patient Safety Agency to issue strong safety guidance in July last year.

NHS trusts were told to agree local action to minimise risks, inform patients, update their prescribing programmes and review all their purchasing of the drug.

However, the chief medical officer, Professor Sir Liam Donaldson, revealed in July that barely half the 500 organisations involved had completed all the actions required even 50 days beyond the March 31 deadline. He suggested this partly reflected the safety culture of the NHS.

News of the two latest deaths emerged in a letter from Wendy Harris, senior pharmacist at the safety agency, to the British Society for Rheumatology. Methotrexate treatment was identified as one of the causes of death of a 57-year-old woman who had been taking the maximum dose weekly for two years. The family of another patient told the agency their relative's death certificate said death had been due to "lung problems as a result of taking methotrexate for arthritis".

Ms Harris asked the society to alert its members and stress that patients should be advised of the risk, monitored, and that doctors should withdraw the drug in the event of methotrexate-induced inflammation of the lungs.